A novel acidic microenvironment microsphere for enhanced bioavailability of carvedilol: Comparison of solvent evaporated and surface-attached system

The purpose of this study was to improve the aqueous solubility and oral bioavailability of practically water-insoluble carvedilol using pH-modulating drug delivery systems. Since carvedilol is weakly basic, its aqueous solubility increases when the drug is surrounded by an acidic microenvironment. Two different microspheres with acidic microenvironment, solvent-evaporated (ASE) and surface-attached (ASA) systems, were prepared in this study using ethanol and distilled water as solvents, respectively. Tartaric acid was selected as the acidifier due to high solubility and excellent compatibility with the drug. ASE microspheres and ASA microspheres were composed of drug/Kollidon® VA64/Tween® 80/tartaric acid at a weight ratio of 1/10/0.5/1 and 1/0.7/0.3/1, respectively. The physicochemical properties of ASE microspheres were consistent; however, ASA microspheres exhibited distinct DSC thermogram and PXRD pattern related to their respective conventional systems. These results can be attributed to partial dissolution of the drug in ASA microspheres due to its pH-dependent solubility behaviour. Both microspheres significantly increased the drug solubility by 5319-fold and 331-fold, respectively, compared to the drug itself (p < 0.05). Moreover, the dissolution rate and oral bioavailability of both formulations was significantly higher than that of the drug (p < 0.05), with ASE being superior to ASA microspheres. Therefore, ASE system is suggested as an optimised pH-modulating drug delivery system for practically water-insoluble carvedilol.